Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers

Hoon, Jan de; Hecken, Anne Van; Vandermeulen, Corinne; Herbots, Marissa; Kubo, Yumi; Lee, Ed; Eisele, Osa; Vargas, Gabriel; Gabriel, Kristin

doi:10.1177/0333102418776017

Cited by 37 publications

(32 citation statements)

References 44 publications

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“…A lack of BP‐increasing effects after CGRP‐inhibition is supported by studies with small‐molecule CGRP receptor antagonists, where there is no evidence of vasoconstriction after CGRP receptor blockade . Further, there was no additional increase in BP observed with erenumab in a recent study with the primary objective to evaluate the safety of concomitant use of sumatriptan and erenumab …”

Section: Discussionmentioning

confidence: 96%

Phase I, Randomized, Double‐blind, Placebo‐controlled, Single‐dose, and Multiple‐dose Studies of Erenumab in Healthy Subjects and Patients With Migraine

Hoon

Hecken

Vandermeulen

et al. 2017

Clin Pharma and Therapeutics

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Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.

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Section: Discussionmentioning

confidence: 96%

Phase I, Randomized, Double‐blind, Placebo‐controlled, Single‐dose, and Multiple‐dose Studies of Erenumab in Healthy Subjects and Patients With Migraine

Hoon

Hecken

Vandermeulen

et al. 2017

Clin Pharma and Therapeutics

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“…36 Furthermore, there was no effect of combination erenumab and sumatriptan on blood pressure compared to sumatriptan alone in a phase 1 study. 37 These studies, in combination with the decrease in triptan use, indicate a lack of effect of erenumab on the effectiveness of triptans as acute migraine treatment, which one would expect triptan use to increase.…”

Section: Discussionmentioning

confidence: 99%

Erenumab in chronic migraine with medication overuse

et al. 2019

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ObjectiveTo determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse.MethodsIn this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3:2:2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving ≥50% reduction from baseline in monthly migraine days.ResultsOf 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] −6.6 [−8.0 to −5.3] and −6.6 [−8.0 to −5.3] vs −3.5 [−4.6 to −2.4]) and acute migraine-specific medication treatment days (−5.4 [−6.5 to −4.4] and −4.9 [−6.0 to −3.8] vs −2.1 [−3.0 to −1.2]). In the placebo and 70 and 140 mg groups, ≥50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36–5.22]) and 35% (odds ratio 2.51 [1.28–4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and health-related quality of life. The observed treatment effects were similar in the non–medication overuse subgroup.ConclusionsErenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.Clinicaltrials.gov identifierNCT02066415.Classification of evidenceThis study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.

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“…Phase 1 trials showed that erenumab was well tolerated, including when combined with triptans; also, cardiovascular safety was demonstrated in patients with stable angina 8‐10 . In other studies, erenumab was well tolerated; injection‐site reactions and constipation were the main adverse effects, affecting approximately 3% of patients 8,9,11‐15 . Phase 2 and phase 3 trials of erenumab as a preventive treatment for episodic migraine with open‐label extension and a phase 2 trial of erenumab for chronic migraine demonstrated a significant reduction in MMD, a 50% responder rate of 30‐65%, and reduced abortive use 12,13,15‐17 …”

Section: Introductionmentioning

confidence: 99%

Real‐World Patient Experience With Erenumab for the Preventive Treatment of Migraine

et al. 2020

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Background.-Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post-market observations are available to validate these findings in a real-world tertiary headache clinic population with complex comorbidities and refractory migraine. Objective.-The goal of this study is to demonstrate the real-world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6 months of erenumab therapy. Methods.-A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140 mg). Baseline data obtained by chart review and telephone calls were compared to 6-month follow-up telephone calls. The primary outcome was the reduction in self-reported headache days per month at baseline compared to 6 months for those with complete 6-month data. The significance level was set at P < .05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing-off, and discontinuation. Results.-Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49 years (range, 19-80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six-month post-erenumab follow-up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5 days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6-month follow-up (P < .001); similarly, the monthly migraine days decreased significantly by 8.4 days from a baseline mean of 19.1 (9.3) days to 10.7 days at 6-month follow-up (P < .001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28). Conclusion.-This post-market observational study of patient experience describes response to erenumab in a real-world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1-week wearing-off resp...

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Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers

Abstract: Co-administration of erenumab and sumatriptan had no additional effect on resting blood pressure or on pharmacokinetics of sumatriptan. Trial registration: ClinicalTrials.gov, NCT02741310.

Cited by 37 publications

References 44 publications

Phase I, Randomized, Double‐blind, Placebo‐controlled, Single‐dose, and Multiple‐dose Studies of Erenumab in Healthy Subjects and Patients With Migraine

Phase I, Randomized, Double‐blind, Placebo‐controlled, Single‐dose, and Multiple‐dose Studies of Erenumab in Healthy Subjects and Patients With Migraine

Erenumab in chronic migraine with medication overuse

Real‐World Patient Experience With Erenumab for the Preventive Treatment of Migraine

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